Produção Nacional
Revisado por pares
Central involvement of kinin B 1 and B 2 receptors in the febrile response induced by endotoxin in rats
1997; Wiley; Volume: 121; Issue: 2 Linguagem: Inglês
10.1038/sj.bjp.0701110
ISSN1476-5381
AutoresM. M. Coelho, C. R. G. C. M. Oliveira, Gisela P. Pajolla, João Β. Calixto, Irene Rosemir Pelá,
Tópico(s)Complement system in diseases
ResumoThe effect of central injection of selective kinin B 1 and B 2 receptor antagonists on the febrile response induced by endotoxin ( E. coli lipopolysaccharide, LPS) in rats was investigated. Intracerebroventricular (i.c.v.) injection of a selective B 2 receptor antagonist (Hoe‐140, 8 nmol) reduced the early (0–2 h), but increased the late phase (4–6 h) of the febrile response induced by intravenous (i.v.) injection of LPS (0.5 μg kg −1 ). Co‐administration of Hoe‐140 (8 nmol, i.c.v.) with LPS (0.5 μg kg −1 , i.v.), followed 2.5 h later by the i.c.v. injection of a selective B 1 receptor antagonist [des‐Arg 9 ‐Leu 8 ]‐bradykinin (BK, 8 nmol), significantly reduced the febrile response induced by LPS throughout the whole experimental period. Intravenous injection of Hoe‐140 (1 mg kg −1 ) significantly reduced the febrile response induced by LPS (0.5 μg kg −1 , i.p.). Pretreatment (24 h) with LPS (0.5 μg kg −1 , i.v.) reduced the febrile response induced by BK or [Tyr 8 ]‐BK (both, 5 nmol, i.c.v.), but markedly increased the febrile response induced by [des‐Arg 9 ]‐BK (5 nmol, i.c.v.). The response induced by [des‐Arg 9 ]‐BK in LPS‐pretreated rats was significantly inhibited by co‐injection of [des‐Arg 9 ‐Leu 8 ]‐BK (15 nmol, i.c.v.). The results suggest that kinins are involved in the induction of LPS‐induced fever and that central B 2 and B 1 receptors are activated during the initial and late phase of this response, respectively. The results also suggest that downregulation and/or desensitization of B 2 receptors and induction and/or upregulation of B 1 receptors in LPS‐pretreated animals may have a significant pathophysiologcal role in the induction and maintenance of fever. These observations may be specifically important in the case of chronic inflammatory conditions, because the BK metabolite [des‐Arg 9 ]‐BK, so far considered an inactive metabolite, acquires an active and relevant role with the progressive expression of B 1 receptors that occurs in such states. British Journal of Pharmacology (1997) 121 , 296–302; doi: 10.1038/sj.bjp.0701110
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